title: Anti-ovulatory effects of RU486 and trilostane involve impaired cyclooxygenase-2 expression and mitotic activity of follicular granulosa cells in rats.
abstract: To explore the mechanism for anti-ovulatory effects of blockade of preovulatory synthesis and action of progesterone, we focused on cyclooxygenase (COX)-2 induction and mitotic activity of granulosa cells in gonadotropins-treated rats. Treatment with RU486 (a progesterone receptor antagonist) or trilostane (a 3β-hydroxysteroid dehydrogenase inhibitor) just prior to or 4h after human chorinonic gonadotropin (hCG) (hCG4h) decreased ovulation rates and circulating progesterone level. Human CG induction of immunoreactive COX-2 in the granulosa layer of mature Graafian follicles at hCG8h was reduced by RU486 treatment at hCG0h and trilostane treatment at hCG4h. RU486 treatment further attenuated ovarian prostaglandin E(2) (PGE(2)) level significantly. Cell proliferative activity in mural granulosa layer of the inhibitors-treated follicles was significantly lower than in intact group. Obtained results show that inhibition of synthesis and action of progesterone caused attenuated COX-2/PGE(2) system and dysregulated mitotic response of granulosa cells, resulting in decreased ovulation.
authors.affiliation: Kitasato University School of Veterinary Medicine, Laboratory of Physiology, Higashi 23-35-1, Towada, Aomori 034-8628 Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mori
authors.forename: Naotaka
authors.initials: N
authors.lastname: Ogino
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Mitsumori
authors.initials: M
authors.lastname: Kawaminami
authors.forename: Shiro
authors.initials: S
authors.lastname: Kurusu
mesh_terms: D000818:Animals; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects* / Q000378:metabolism*; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006063:Chorionic Gonadotropin; D013196:Dihydrotestosterone; D015735:Mifepristone; D011374:Progesterone; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C009954:trilostane